Want to clone a mouse? Don’t use stem cells.

A careful study of cloning using mice as an experimental system suggests that …

The first successful mammalian cloning, that of Dolly the sheep, was done using a technique called somatic cell nuclear transport, or SCNT. This technique involves getting rid of an unfertilized egg cell's nucleus, and then replacing it with one from the cell of an adult. If all goes well, the proteins in the egg reprogram the chromosomes in the new nucleus to think it's an embryo, and the clone is off to the races. The problem is that things rarely go well—the success rate is abysmally low. Some researchers have suggested that this might be due to the donor population of cells not being identical. We've come to realize that most tissues have small populations of stem cells within them, and it was suggested that the stem cells would make better clones, since they were expected to be closer to the embryonic state to start with. Hence, the low frequency of stem cells in the donor tissue would lead to the low success rate.

Researchers have just tested this proposal, and it turns out to be exactly wrong. They used a standard protocol for SCNT in mice, and chose the blood lineage for the donor cells, as it has a very well-characterized lineage of stem cells, precursor cells, and mature blood cells. SCNTs with the stem cells had a 4 percent success rate, while two different precursor states worked 8 and 11 percent of the time. The big surprise, however, came when they used a fully-mature blood cell called a granulocyte. Pulling the nucleus out of a granulocyte and dropping it into an egg led to embryonic development a shocking 35 percent of the time. Apparently, either our expectations for what would work for cloning are going to have to be adjusted, or adult stem cells aren't as close to the embryonic state as we might think.

If stem cells aren't controversial enough, the New York Times is reporting on a story that adds evolution and the US Patent and Trademark Office in to the mix. Much of the work with human embryonic stem cells in the US is limited by broad patents granted to researchers at the University of Wisconsin. In an effort to change that, several groups have convinced the USPTO to reevaluate the patent. Their argument is based on the fact that many of the techniques used in the patent were previously pioneered by other researchers using different mammalian systems, and this work represents prior art. In essence, the USPTO is going to have to decide whether humans are just another mammal (in which case using these techniques on human cells is nothing special) or in some way stand apart from the rest of our furry relatives, at least in terms of patents. The article notes that the case may take years to decide.